Digital imaging technologies have been used in various scientific fields for decades. As science develops, new instruments and techniques for imaging technologies are in great demand. Imaging technologies comprise optical/fluorescence imaging, x-ray imaging, magnetic resonance imaging (MRI), ultrasound, microwave, X-ray computed tomography (CT), positron emission tomography (PET) or single photon emission computed tomography (SPECT).
Bioimaging describes imaging technologies to study the integrative functions of biological molecules, cells, organ systems and whole organisms. Imaging technologies make use of molecular probes or interactions with molecules.
Advanced, multimodal imaging techniques, powered by new computational methods, are also available. These new imaging technologies allow examination of anatomical structures linked to functional data, as described by electric and magnetic fields, mechanical motion, and metabolism.
Bioimaging is useful for but not limited to in vivo diagnostics, visualization of drug delivery and cell staining. Biological pathways and processes can also be visualized.
Nanoparticles of uniform size and shape (preferably 3-5 nm diameter) have been proven an effective tool for bioimaging. Nanoparticles have a high area-to-volume ratio; they are very reactive, good catalysts and adhere to biological molecules. A preferred material is silicon as it is inert, non-toxic, abundant and economic. The silicon surface can be functionalized. Silicon nanoparticles show efficient photoluminescence in the visible part of the electromagnetic spectrum and are bioinert and chemically stable. The only material which has similar biocompatibility is porous silicon. Particles smaller than 100 nm show an enhanced permeability and retaining effect (EPR effect) in tumours, an important nonspecific targeting effect.
Silicon nanoparticles, also known as silicon quantum dots, can be used in imaging technologies but also for LED, photovoltaics, lithium ion batteries, transistors, polymers or two-photon absorption.
Efficient coupling of silicon nanoparticles to nucleotides has been shown by Wang et al. (Bioconjug. Chem. 2004; 15:409-12). Thereby nucleotides acquire a luminescent label. It has also been shown that silicon quantum dots can be coupled to streptavidin which retains their binding capability to biotin. Blue emission is retained in the silicon quantum dot-protein complex (Choi et al.: Bioconjug. Chem. 2008; 19:680-85).
Labelling of cancer cells has been described by Erogbogbo et al. (Bioconjug. Chem. 2011; 22(6):1081-8). Silicon quantum dots were conjugated to lysine, folic acid, antimesothelin or apo-transferrin for cellular labeling.
However, an important safety concern regarding toxicity of nanoparticles remains. Cytotoxicity and imaging properties of silicon quantum dots have been studied by Fujioka et al. They have shown efficient labeling of HeLa cells and less toxicity compared with cadium based quantum dots (Nanotechnology 2008; 19(41):415102).
Choi et al. have studied toxicity as well as inflammatory potential of silicon nanoparticles compared with silicon microparticles. While microparticles (10 to 3,000 nm) are less cytotoxic when compared at the same concentrations, silicon nanoparticles (3 nm) have shown a significantly lower cytotoxicity per particle. They also showed low inflammatory responses at high concentrations (Choi et al.: J. Appl. Toxicol. 2009; 29:52-60).
Despite numerous studies Rivolta et al. emphasize that silicon nanoparticles still need to reach a better stability in physiological media and more toxicity studies are necessary (BONSAI Project Symposium; AIP Conference Proceedings 2010; 1275:94-97).
Tu et al. studied biocompatibility and plasma clearance of dextran-coated 64Cu-DO3A conjugated silicon nanoparticles by PET. Both biocompatibility and plasma clearance are important parameters for clinical application. While the nanoparticles were also excreted from the body via renal filtration and urinary bladder, they mainly accumulated in the liver (ACS Med. Chem. Lett. 2011, 2:285-288).